Matching Patients to Accelerate Clinical Trials (MPACT): Enabling Technology for Oncology Clinical Trial Workflow.

Clinical trial enrollment is impeded by the significant time burden placed on research coordinators screening eligible patients. With 50,000 new cancer cases every year, the Veterans Health Administration (VHA) has made increased access for Veterans to high-quality clinical trials a priority. To aid in this effort, we worked with research coordinators to build the MPACT (Matching Patients to Accelerate Clinical Trials) platform with a goal of improving efficiency in the screening process. MPACT supports both a trial prescreening workflow and a screening workflow, employing Natural Language Processing and Data Science methods to produce reliable phenotypes of trial eligibility criteria. MPACT also has a functionality to track a patient's eligibility status over time. Qualitative feedback has been promising with users reporting a reduction in time spent on identifying eligible patients.

Effect of Pharmacogenetic Testing for Statin Myopathy Risk vs Usual Care on Blood Cholesterol: A Randomized Clinical Trial.

Importance: Nonadherence to statin guidelines is common. The solute carrier organic anion transporter family member 1B1 (SLCO1B1) genotype is associated with simvastatin myopathy risk and is proposed for clinical implementation. The unintended harms of using pharmacogenetic information to guide pharmacotherapy remain a concern for some stakeholders. Objective: To determine the impact of delivering SLCO1B1 pharmacogenetic results to physicians on the effectiveness of atherosclerotic cardiovascular disease (ASCVD) prevention (measured by low-density lipoprotein cholesterol [LDL-C] levels) and concordance with prescribing guidelines for statin safety and effectiveness. Design, Setting, and Participants: This randomized clinical trial was performed from December 2015 to July 2019 at 8 primary care practices in the Veterans Affairs Boston Healthcare System. Participants included statin-naive patients with elevated ASCVD risk. Data analysis was performed from October 2019 to September 2020. Interventions: SLCO1B1 genotyping and results reporting to primary care physicians at baseline (intervention group) vs after 1 year (control group). Main Outcomes and Measures: The primary outcome was the 1-year change in LDL-C level. The secondary outcomes were 1-year concordance with American College of Cardiology-American Heart Association and Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for statin therapy and statin-associated muscle symptoms (SAMS). Results: Among 408 patients (mean [SD] age, 64.1 [7.8] years; 25 women [6.1%]), 193 were randomized to the intervention group and 215 were randomized to the control group. Overall, 120 participants (29%) had a SLCO1B1 genotype indicating increased simvastatin myopathy risk. Physicians offered statin therapy to 65 participants (33.7%) in the intervention group and 69 participants (32.1%) in the control group. Compared with patients whose physicians did not know their SLCO1B1 results at baseline, patients whose physicians received the results had noninferior reductions in LDL-C at 12 months (mean [SE] change in LDL-C, -1.1 [1.2] mg/dL in the intervention group and -2.2 [1.3] mg/dL in the control group; difference, -1.1 mg/dL; 90% CI, -4.1 to 1.8 mg/dL; P < .001 for noninferiority margin of 10 mg/dL). The proportion of patients with American College of Cardiology-American Heart Association guideline-concordant statin prescriptions in the intervention group was noninferior to that in the control group (12 patients [6.2%] vs 14 patients [6.5%]; difference, -0.003; 90% CI, -0.038 to 0.032; P < .001 for noninferiority margin of 15%). All patients in both groups were concordant with CPIC guidelines for safe statin prescribing. Physicians documented 2 and 3 cases of SAMS in the intervention and control groups, respectively, none of which was associated with a CPIC guideline-discordant prescription. Among patients with a decreased or poor SLCO1B1 transporter function genotype, simvastatin was prescribed to 1 patient in the control group but none in the intervention group. Conclusions and Relevance: Clinical testing and reporting of SLCO1B1 results for statin myopathy risk did not result in poorer ASCVD prevention in a routine primary care setting and may have been associated with physicians avoiding simvastatin prescriptions for patients at genetic risk for SAMS. Such an absence of harm should reassure stakeholders contemplating the clinical use of available pharmacogenetic results. Trial Registration: ClinicalTrials.gov Identifier: NCT02871934.

Pragmatic Trials in Genomic Medicine: The Integrating Pharmacogenetics In Clinical Care (I-PICC) Study.

Pragmatic clinical trials (PCTs) have an established presence in clinical research and yet have only recently garnered attention within the landscape of genomic medicine. Using the PRagmatic-Explanatory Continuum Indicator Summary 2 (PRECIS-2) as a framework, this paper illustrates the application of PCT principles to The Integrating Pharmacogenetics In Clinical Care (I-PICC) Study, a trial of pharmacogenetic testing prior to statin initiation for cardiovascular disease prevention in primary care. The trial achieved high engagement with providers (85% enrolled of those approached) and enrolled a representative sample of participants for which statin therapy would be recommended. The I-PICC Study has a high level of pragmatism, which should enhance the generalizability of its findings. The PRECIS-2 may be useful in the design and evaluation of PCTs of genomic medicine interventions, contributing to the generation of evidence that can bridge the gap between genomics innovation and clinical adoption.

The Integrating Pharmacogenetics in Clinical Care (I-PICC) Study: Protocol for a point-of-care randomized controlled trial of statin pharmacogenetics in primary care.

BACKGROUND: The association between the SLCO1B1 rs4149056 variant and statin-associated muscle symptoms (SAMS) is well validated, but the clinical utility of its implementation in patient care is unknown. DESIGN: The Integrating Pharmacogenetics in Clinical Care (I-PICC) Study is a pseudo-cluster randomized controlled trial of SLCO1B1 genotyping among statin-naïve primary care and women's health patients across the Veteran Affairs Boston Healthcare System. Eligible patients of enrolled primary care providers are aged 40-75 and have elevated risk of cardiovascular disease by American College of Cardiology/American Heart Association (ACC/AHA) guidelines. Patients give consent by telephone in advance of an upcoming appointment, but they are enrolled only if and when their provider co-signs an order for SLCO1B1 testing, performed on a blood sample already collected in clinical care. Enrolled patients are randomly allocated to have their providers receive results through the electronic health record at baseline (PGx + arm) versus after 12 months (PGx- arm). The primary outcome is the change in low-density lipoprotein cholesterol (LDL-C) after one year. Secondary outcomes are concordance with Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for simvastatin prescribing, concordance with ACC/AHA guidelines for statin use, and incidence of SAMS. With 408 patients, the study has >80% power to exclude a between-group LDL-C difference of 10 mg/dL (non-inferiority design) and to detect between-group differences of 15% in CPIC guideline concordance (superiority design). CONCLUSION: The outcomes of the I-PICC Study will inform the clinical utility of preemptive SLCO1B1 testing in the routine practice of medicine, including its proposed benefits and unforeseen risks.

Molecularly Designed Stabilized Asymmetric Hollow Fiber Membranes for Aggressive Natural Gas Separation.

New rigid polyimides with bulky CF3 groups were synthesized and engineered into high-performance hollow fiber membranes. The enhanced rotational barrier provided by properly positioned CF3 side groups prohibited fiber transition layer collapse during cross-linking, thereby greatly improving CO2 /CH4 separation performance compared to conventional materials for aggressive natural gas feeds.

Somatic dysfunction and use of osteopathic manual treatment techniques during ambulatory medical care visits: a CONCORD-PBRN study.

CONTEXT: Osteopathic manual treatment (OMT) of somatic dysfunction is a unique approach to medical care that may be studied within a practice-based research network. OBJECTIVE: To measure patient characteristics and osteopathic physician practice patterns within the Consortium for Collaborative Osteopathic Research Development-Practice-Based Research Network (CONCORD-PBRN). DESIGN: Cross-sectional card study. SETTING: Eleven member clinics within the CONCORD-PBRN coordinated by The Osteopathic Research Center. PATIENTS: A total of 668 patients seen between January and March 2013. MAIN STUDY MEASURES: Patient age and sex; primary diagnoses; somatic dysfunction as manifested by tenderness, asymmetry, restricted motion, or tissue texture changes; and use of 14 OMT techniques. Results were stratified by anatomical region and adjusted for clustering within member clinics. Clustering was measured by the intracluster correlation coefficient. RESULTS: Patient ages ranged from 7 days to 87 years (adjusted mean age, 49.2 years; 95% confidence interval [CI], 43.3-55.1 years). There were 450 females (67.4%) and 508 patient visits (76.0%) involved a primary diagnosis of disease of the musculoskeletal system and connective tissue. Structural examination was performed during 657 patient visits (98.4%), and 649 visits (97.2%) involved OMT. Restricted motion and tenderness were the most and least common palpatory findings, respectively. Cranial (1070 [14.5%]), myofascial release (1009 [13.7%]), muscle energy (1001 [13.6%]), and counterstrain (980 [13.3%]) techniques were most commonly used, accounting for more than one-half of the OMT provided. Pediatric patients were more likely than adults to receive OMT within the head (adjusted odds ratio [OR], 9.53; 95% CI, 1.28-71.14). Geriatric patients were more likely than adults to receive a structural examination (adjusted OR, 1.83; 95% CI, 1.09-3.07) and OMT (adjusted OR, 1.62; 1.02-2.59) within the lower extremity. Females were more likely than males to receive a structural examination (adjusted OR, 2.44; 95% CI, 1.44-4.16) and OMT (adjusted OR, 2.11; 95% CI, 1.26-3.52) within the sacrum and OMT within the pelvis (adjusted OR, 1.79; 95% CI, 1.12-2.88). Intracluster correlation coefficients for the 4 most commonly used OMT techniques ranged from 0.34 to 0.72. CONCLUSION: This study provides proof of concept of the feasibility of studying osteopathic medical practice on a national level by developing and growing the CONCORD-PBRN.

Depolymerization and hydrodeoxygenation of switchgrass lignin with formic acid.

Organosolv switchgrass lignin is depolymerized and hydrodeoxygenated with a formic acid hydrogen source, 20 wt % Pt/C catalyst, and ethanol solvent. The combination of formic acid and Pt/C is found to promote production of higher fractions of lower molecular weight compounds in the liquid products. After 4 h of reaction, all of the switchgrass lignin is solubilized and 21 wt % of the biomass is shown to be converted into seven prominent molecular species that are identified and quantified. Reaction time is shown to be an important variable in affecting changes in product distributions and bulk liquid product properties. At 20 h of reaction, the lignin is significantly depolymerized to form liquid products with a 76 % reduction in the weighted average molecular weight. Elemental analysis also shows that the resultant liquid products have a 50 % reduction in O/C and 10 % increase in H/C molar ratios compared to the switchgrass lignin after 20 h.

Stenosing synovitis of the extensor pollicis longus tendon.

There are only a few published cases of extensor pollicis longus (EPL) tenosynovitis in patients without rheumatoid arthritis. Even less common are cases of stenosing tenosynovitis of the EPL associated with triggering. This article presents 2 cases of EPL stenosing tenosynovitis with triggering of the thumb in the area of Lister's tubercle and addresses how to treat them.

Effects of organosolv pretreatment and enzymatic hydrolysis on cellulose structure and crystallinity in Loblolly pine.

Ethanol organosolv pretreatment was performed on Loblolly pine to enhance the efficiency of enzymatic hydrolysis of cellulose to glucose. Solid-state (13)C NMR spectroscopy coupled with line shape analysis was used to determine the structure and crystallinity of cellulose isolated from pretreated and enzyme-hydrolyzed Loblolly pine. The results indicate reduced crystallinity of the cellulose following the organosolv pretreatment, which renders the substrate easily hydrolyzable by cellulase. The degree of crystallinity increases and the relative proportion of para-crystalline and amorphous cellulose decreases after enzymatic hydrolysis, indicating preferential hydrolysis of these regions by cellulase. The structural and compositional changes in this material resulting from the organosolv pretreatment and cellulase enzyme hydrolysis of the pretreated wood were studied with solid-state CP/MAS (13)C NMR spectroscopy. NMR spectra of the solid material before and after the treatments show that hemicelluloses and lignin are degraded during the organosolv pretreatment.

Hydrodeoxygenation and coupling of aqueous phenolics over bifunctional zeolite-supported metal catalysts.

Pt supported on HY zeolite is successfully used as a bifunctional catalyst for phenol hydrodeoxygenation in a fixed-bed configuration at elevated hydrogen pressures, leading to hydrogenation-hydrogenolysis ring-coupling reactions producing hydrocarbons, some with enhanced molecular weight.

Hammer toe correction by arthrodesis of the proximal interphalangeal joint using a cortical bone allograft pin.

In hammer toe correction by means of digital fusion, fixation so that the bone can unite while maintaining appropriate realignment can be a challenge. Metal fixation pins can be associated with many problems and potential complications. The author presents a method of rigid internal fixation using 2.4-mm-diameter pins fashioned out of freeze-dried allogeneic cortical bone. These devices avoid most of the risks of metal pins. Proximal interphalangeal joint arthrodesis using cortical bone pins was performed on 26 toes in 18 patients with very few complications. The author concludes that use of cortical bone pins can yield successful results in most cases. The outcomes of the fusions can be further enhanced by using flexor digitorum longus tendon transfer.